NUCALA® Special Drug Use Investigation (EGPA, Long-term): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NUCALA® Special Drug Use Investigation (EGPA, Long-term) (NCT03557060), a registered phase not stated study. The primary outcome is Number of Participants With Adverse Drug Reactions (ADRs).

2. Clinical Question

3. Trial Design

This is a drug use investigation of NUCALA in EGPA, rather than a randomized comparison. Participants received NUCALA in clinical practice. The registry does not state how allocation would have occurred, and it explicitly cautions that the arms are not a like-for-like control comparison. A control-group effect estimate should not be inferred from these details.

The brief description frames the program as collecting information on safety and effectiveness during long-term use. It says participants would be followed for up to 96 weeks from the start of NUCALA administration for EGPA, or until treatment withdrawal or termination. For participants who stopped because symptoms improved, an additional 48 weeks of follow-up was to be conducted as much as possible. The described total study duration was approximately 3 years, including the observation and follow-up periods.

The registry lists enrollment as 4115. The brief description also says approximately 300 participants would be included. These figures differ, and the reason for the difference is not reported in the registry record. The safety analysis population is described as participants with locked case report forms who did not meet the safety-analysis exclusion criteria; the posted safety figures use 836 participants at risk.

The record lists a start date of 2018-06-25, a primary completion date of 2025-07-30, and a status of COMPLETED. It identifies GlaxoSmithKline as the sponsor. Although the stated objective includes effectiveness, the available details do not specify an effectiveness endpoint or a comparative effectiveness analysis. The registry record does not report a detailed protocol for analysis, a sample-size justification, or interim analyses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 4115 participants were enrolled in the study; however, 836 participants were included in Safety Analysis Population. Safety Analysis Population consisted of the participants with locked case report form \[CRF\]. It includes participants that do not fall under the safety analysis exclusion criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Population which consisted of the participants with locked case report form (CRFs). It includes participants that do not fall under the safety analysis exclusion criteria.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Baseline characteristics were reported for Safety Analysis Population which consisted of the participants with locked case report form (CRFs). It includes participants that do not fall under the safety analysis exclusion criteria.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Drug Reactions (ADRs), measured over Up to 96 Weeks.

The primary endpoint is the number of participants with adverse drug reactions (ADRs), with the unit recorded as participants and the timeframe given as up to 96 Weeks. An ADR is defined as an adverse event for which a causal relationship with the drug was not ruled out. This definition concerns the assessment of a possible relationship to treatment; it does not mean that every reported event is established as caused by NUCALA.

Counting participants with an event is a binary-outcome approach: each participant is classified according to whether at least one qualifying event occurred during the stated observation period. Such counts can communicate how many participants experienced an event, but they do not describe event severity, duration, recurrence, or timing unless those details are separately reported. The primary endpoint is used to organize safety monitoring around events considered possibly related to the drug.

The endpoint population is the safety analysis population, defined as participants with locked case report forms who did not fall under the safety-analysis exclusion criteria. The posted adverse-event summary includes counts for serious and other adverse events, but those figures are not explicitly identified as the primary ADR result. A separate numerical result for the number of participants with ADRs is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a count of participants with ADRs, not a count of all individual event episodes. General statistical explanation: for a binary outcome, a participant is typically classified as having or not having the defined event during the specified period. A participant with repeated events may still contribute as one participant with an event to a participant-count endpoint. The registry does not describe how recurrent events were handled beyond naming the endpoint as a number of participants.

The endpoint's event definition combines clinical event reporting with a causality judgment: an ADR is an adverse event for which a causal relationship with the drug was not ruled out. This is not the same as saying that causation is certain. General explanation: causality assessments can be uncertain, and the recorded category reflects the stated rule for inclusion. The available record does not describe who made those assessments, what criteria were used, or whether assessments were independently reviewed.

How should serious and other event counts be read?

The adverse-event summary separates serious events from other events. It reports 836 at risk and 15 affected for serious events, and 836 at risk and 46 affected for other events. These are descriptive results for the listed population. The record does not provide a randomized treatment comparison, and the registry cautions that the arms are not like-for-like controls. Thus, the counts should not be read as an estimate of a relative treatment effect.

General statistical explanation: event counts can be useful for describing the observed safety experience, but interpretation depends on the denominator, observation time, completeness of reporting, and the definition of an event. Counts alone do not indicate whether the event was caused by the drug. Nor do they show how long events lasted, whether participants experienced more than one event, or how risk changed over time. Those details are not reported in the registry record.

What do the analyses tell us?

The registry lists zero analyses. No inferential test, adjusted estimate, confidence interval, or model specification is reported. As a result, there is no reported statistical estimate of uncertainty around the event counts and no formal test of a treatment contrast. General explanation: a confidence interval is a way to express the precision of an estimate under a stated statistical method. Without one, the observed count remains descriptive and should not be presented as a precise estimate of a broader population rate.

The record includes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it describes the target effect as a stated fraction of the observed effect. These are planning assumptions, not evidence that the investigation used a two-arm randomized design. The registry expressly says allocation is not stated and that the arms do not represent a like-for-like control comparison. Any planning sample sizes are illustrations, not observed power. The record does not report the trial's own sample-size justification.

Why does observation time matter?

The primary endpoint timeframe is up to 96 Weeks. The brief description says follow-up could end earlier if NUCALA administration was withdrawn or terminated, and it describes an additional 48 weeks of follow-up for participants stopping due to symptom improvement, as much as possible. General statistical explanation: when participants have different lengths of observation, a simple count does not account for person-time or establish when events occurred. Time-to-event methods can address timing and differing follow-up under specified assumptions, but the registry does not report such an analysis for this endpoint.

The brief description's intended observation plan and the posted analysis population are not identical concepts. The former describes the intended follow-up; the latter is defined by locked case report forms and exclusion criteria. The record does not report how many participants completed each follow-up period, how missing observations were handled, or whether follow-up differed across participants. Those omissions limit assessment of how completely the counts capture events over time.

What cannot be inferred from this design?

Without a stated randomized allocation and an appropriate comparable control group, the event counts cannot isolate the effect of NUCALA from other influences. General explanation: uncontrolled observational data may reflect differences in participants, clinical practice, follow-up, or event recording. This does not invalidate descriptive reporting, but it limits causal interpretation. The registry does not report enough detail to determine whether any adjustment for such factors was planned or performed.

The registry's primary safety definition and its serious-event listing answer related but distinct questions. Seriousness is a classification of an event; an ADR is defined by a causal relationship not being ruled out. The available details do not identify which listed serious events met the ADR definition. Consequently, the serious-event counts should not be substituted for a numerical primary endpoint result.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Participants With EGPA")
n      <- c(836)
events <- c(57)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Participants With EGPA  836  57  6.8  5.2  8.7  5.3  8.7  5.3  8.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and zero analyses. It does not report a multiplicity strategy, such as how statistical error would be controlled across multiple endpoints or comparisons. Because no inferential analyses are listed, the record also provides no reported hypothesis-testing plan or adjustment for multiple testing. The absence of a stated plan should not be filled in by assumption.

Missing-data handling is not reported in the registry record. The brief description specifies an intended observation period of up to 96 weeks, possible earlier end of observation after treatment withdrawal or termination, and an additional 48 weeks of follow-up after stopping due to symptom improvement as much as possible. It does not state how incomplete follow-up, missing case-report-form entries, or participants without complete observation were treated in the outcome summaries.

The safety analysis population consists of participants with locked case report forms who do not meet the safety-analysis exclusion criteria. The registry does not describe the exclusion criteria or give a flow of participants into and out of this population. The adverse-event summary lists 836 participants at risk in each category; the enrollment field lists 4115, while the brief description refers to approximately 300 participants. The record does not explain the relationship among these figures.

General statistical explanation: analysis populations and missing-data rules affect which participants contribute to an estimate and what that estimate represents. If follow-up or event recording is incomplete, counts may not represent the same observation experience for every participant. Without details on exclusions, missingness, or sensitivity analyses, the robustness of the reported summaries cannot be assessed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: eosinophilic granulomatosis with polyangiitis (0.5%), condition aggravated (0.1%), death (0.1%), herpes zoster (0.1%), pneumonia (0.1%).

The serious-event summary lists 836 participants at risk and 15 affected. The separate other-event summary lists 836 at risk and 46 affected. The group summary also records 1 death. These figures describe the registry's adverse-event reporting; they are not a comparison with an untreated or randomized control group.

The serious-event term listing reports Eosinophilic granulomatosis with polyangiitis at 0.5%, Condition aggravated at 0.1%, Death at 0.1%, Herpes zoster at 0.1%, Pneumonia at 0.1%, and Pneumonia cytomegaloviral at 0.1%. The terms are presented as serious-event terms, while the primary endpoint is specifically the number of participants with ADRs. A serious event is not automatically an ADR, because the primary endpoint also depends on whether a causal relationship with the drug was not ruled out. The record does not provide a mapping between these categories.

General statistical explanation: event terms and participant counts may represent different ways of grouping safety information. The record does not state whether listed terms are mutually exclusive, whether participants could contribute to more than one term, or how the displayed percentages were derived. These summaries should therefore be read as descriptive registry entries, not as evidence of causation or as a complete measure of all safety outcomes.

13. What the Result Does, and Does Not, Mean

The results describe safety information recorded for participants with EGPA receiving NUCALA in clinical practice. The registry identifies the primary safety outcome as the number of participants with ADRs during up to 96 Weeks, using the definition that an adverse event qualifies when a causal relationship with the drug was not ruled out. The available adverse-event summary reports serious and other event counts and lists selected serious-event terms.

These figures do not establish that NUCALA caused any particular event. The ADR definition itself allows for uncertainty in the causal assessment, and the serious-event classification is not equivalent to the ADR classification. The registry does not provide a separate numerical result for the primary ADR endpoint or explain how serious-event terms correspond to it. It also does not report an inferential analysis or a controlled comparison.

The study is not described as randomized, allocation is not stated, and the registry warns that the arms are not a like-for-like control comparison. As a result, the posted counts cannot be interpreted as evidence that one treatment produces more or fewer events than another. They also cannot establish a causal effect of treatment, estimate comparative effectiveness, or settle how outcomes would differ under another care strategy.

General statistical explanation: descriptive counts tell readers what was recorded in a defined population, while estimates of comparative effects require a design and analysis that support the comparison. Precision also depends on uncertainty estimates and on the completeness and duration of follow-up. No confidence interval or formal uncertainty analysis is reported for these counts. The difference between the enrollment listing of 4115, the brief description's approximately 300 participants, and the safety summary's 836 at risk is not explained in the registry record.

The record's completed status and long-term follow-up description establish the context of the investigation, but they do not resolve these interpretation limits. The findings are best understood as registry safety summaries from a clinical-practice investigation, not as a randomized estimate of efficacy or a definitive causal safety assessment.

14. Why This Trial Matters Statistically

This investigation is statistically relevant because it illustrates the distinction between collecting safety information in clinical practice and estimating a treatment effect in a controlled comparison. Its stated objective is to assess long-term safety and effectiveness of NUCALA SC injection in EGPA, while the registry cautions that the arms are not like-for-like controls and does not state allocation. That design context shapes what the observed counts can support.

The primary endpoint also highlights the importance of definitions. The outcome counts participants with ADRs, where an ADR is an adverse event for which a causal relationship with the drug was not ruled out. The posted serious-event counts and event terms are related safety information, but they should not automatically be treated as the primary ADR result. Distinguishing event occurrence, seriousness, and suspected causality is essential when interpreting clinical safety records.

The record also shows why population definitions and denominators matter. It lists enrollment as 4115, describes approximately 300 participants in its brief summary, and reports 836 at risk in the safety summary. These values refer to different parts of the record, and their relationship is not explained. The safety analysis population is defined by locked case report forms and exclusion criteria, but those criteria are not detailed.

Finally, zero analyses are listed, and no inferential estimates or missing-data methods are reported. These absences limit assessment of precision and robustness. General statistical lesson: clear outcome definitions, transparent population flow, complete follow-up reporting, and an analysis suited to the design are necessary for readers to judge how far descriptive safety findings can be generalized or compared.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The record does not state allocation, and it warns that the arms are not a like-for-like control comparison. This limits causal interpretation and prevents the adverse-event counts from serving as a controlled estimate of treatment effect. The registry does not report a detailed statistical analysis plan, a sample-size justification, or interim analyses.

Although the stated objective includes effectiveness, the available outcome information centers on safety. The record lists three outcome measures but no analyses. It does not provide a separate numerical result for the primary endpoint, the number of participants with ADRs. The serious and other adverse-event summaries cannot be assumed to represent that endpoint because the ADR definition and seriousness classification are distinct.

Population figures are not reconciled: enrollment is listed as 4115, the brief description says approximately 300 participants, and the safety summary lists 836 at risk. The record does not explain these differences. It defines the safety population through locked case report forms and exclusion criteria but does not describe those criteria or provide participant flow.

Follow-up could extend up to 96 weeks, with earlier termination in some circumstances and an additional 48 weeks of follow-up for participants stopping due to symptom improvement as much as possible. The record does not report actual follow-up completion, event timing, missing-data handling, or how participants with incomplete records were treated. It also does not specify how adverse-event causality was assessed or whether event terms could overlap across participants.

These limitations mean the posted counts should be interpreted as descriptive registry information. They do not provide a complete basis for judging precision, missing-data sensitivity, comparative effectiveness, or causal safety effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: NUCALA® Special Drug Use Investigation (EGPA, Long-term) — NCT03557060.
• Registry record last updated 2026-02-18; status last verified 2026-01.
• Results first posted 2026-02-18.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT03557060 is titled NUCALA® Special Drug Use Investigation (EGPA, Long-term), sponsored by GlaxoSmithKline. The registry lists the study as COMPLETED, with a start date of 2018-06-25 and primary completion date of 2025-07-30. The investigation concerns NUCALA subcutaneous injection for EGPA in clinical practice.

The stated primary endpoint is the number of participants with adverse drug reactions during up to 96 Weeks. The registry defines an ADR as an adverse event for which a causal relationship with the drug was not ruled out. Its safety summary lists 836 participants at risk and 15 affected for serious events, 836 at risk and 46 affected for other events, and 1 death. The record lists zero analyses and does not provide a separate numerical result for the primary ADR endpoint.

The registry lists enrollment as 4115, while the brief description refers to approximately 300 participants; the reason for the difference is not reported in the registry record. Allocation is not stated, and the record cautions that the arms are not like-for-like control groups. The posted information is therefore descriptive and does not constitute a randomized treatment comparison.